An individual is constantly at risk for chronic infections by a variety of agents such as viruses, bacteria, fungi, protozoa and multicellular parasites. Some of the associated infectious diseases are seriously disabling or even life-threatening. Opportunistic infections caused by eukaryotic organisms such as fungi, protozoa and multicellular parasites present a particular challenge for antibiotic agent development because of the evolutionarily shared cellular processes in all eukaryotic cells including human and other animal cells.
Parasitic protozoa are responsible for a wide variety of infections in man and animals. Many of the diseases are life threatening to the host and cause considerable economic loss in animal husbandry. For example, malaria remains a significant health threat to humans despite massive international attempts to eradicate the disease; trypanosomiasis such as Chagas disease caused by Trypanosoma cruzi and African sleeping sickness caused by T. brucei are not uncommon in Africa and South America; and opportunistic infections in immunocompromised hosts caused by Pneumocystis carinii, Toxoplasma gondii, Cryptosporidium sp. are becoming increasingly significant in the developed countries.
A protozoal infection of great economic importance is coccidiosis, a widespread disease of domesticated animals produced by infections by protozoa of the genus Eimeria. Some of the most significant of Eimeria species are those in poultry namely E. tenella, E. acervulina, E. necatrix, E. brunetti and E. maxima. The disease is responsible for high levels of morbidity and mortality in poultry and can result in extreme economic losses. In some protozoal diseases, such as Chagas disease, there is no satisfactory treatment; in others, drug-resistant strains of the protozoa may develop.
In addition to parasitic protozoa infections, there exist a myriad of opportunistic mycotic infections caused by such agents as Cryptococcus spp., Candida spp., Aspergillus spp., Histoplasma spp., Coccidioides spp., Paracoccidioides spp. Blastomyces spp., Fusarium spp., Sporothrix spp., Trichosporon spp., Rhizopus spp., Pseudallescheria spp., dermatophytes, Paeciliomyces spp., Alternaria spp., Curvularia spp., Exophiala spp., Wangiella spp., Penicillium spp., Saccharomyces spp., Dematiaceous fungi and Pneumocystis carinii. Many of the present treatments cause severe side effects and some of the currently available antibiotic agents are only fungistatic.
Accordingly, there exists a continued need to identify new and effective antibiotic or antipathogenic drugs. However, antibiotic drug discovery has been, for the most part, a random and laborious process through biological screening of natural products and synthetic compounds against a panel of parasites or fungi. This process can be greatly facilitated and made more specific if a target of antibiotic agents can be identified, and incorporated into a screening process for antibiotic agents. There is a need in the art for new drug targets to identify novel, effective antibiotic agents. Once such agents are identified, treatment of opportunistic infections may be achieved.